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The TRPC Family of TRP Channels: Roles Inferred (Mostly) from Knockout Mice and Relationship to ORAI Proteins

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Mammalian Transient Receptor Potential (TRP) Cation Channels

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 223))

Abstract

Aside from entering into cells through voltage gated Ca channels and Na/Ca exchangers in those cells that express these proteins, for all cells be they excitable or non-excitable, Ca2+ enters through channels that are activated downstream of phosphoinositide mobilization (activation of phospholipase C, PLC) and through channels that are activated secondary to depletion of internal stores. Depletion of internal stores activates plasma membrane channels known as ORAIs. Activation of PLCs activates the canonical class of transient receptor potential channels (TRPCs), and, because this activation also causes depletion of Ca2+ stores, also ORAI based channels. Whereas the activation of ORAI is a well-accepted phenomenon, it appears that TRPC channels also participate in Ca2+ entry triggered by store depletion with or without participation of ORAI molecules. Regardless of molecular makeup of TRPC containing channels, a plethora of studies have shown TRPCs to be important both in physiologic systems as well as in pathophysiologic phenomena. Particularly important in defining roles of TRPCs, have been studies with mice with targeted disruption of their genes, i.e., with TRPC KO mice. In this chapter we first focus on TRPCs as regulators of body functions in health and disease, and then focus on the possible make-up of the channels of which they participate. A hypothesis is set forth, whereby ORAI dimers are proposed to be regulatory subunits of tetrameric TRPC channels and serve as structural units that form ORAI channels either as dimers of dimers or trimers of dimers.

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Abbreviations

CaCaM:

Ca2+-calmodulin complex

DAG:

Diacylglycerol

ER:

Endoplasmic reticulum

GPCR:

G protein coupled receptor

IP3:

Inositol 1,4,5-trisphosphate

OAG:

Oleyl-acetyl-glycerol

PLC:

Phospholipase C

PM:

Plasma membrane

PMCA:

Plasma membrane Ca2+-activated ATPase

ROC:

Receptor operated channel

ROCE:

Receptor operated Ca2+ entry

SERCA:

Sarcoplasmic endoplasmic reticulum Ca2+-activated ATPase

SOC:

Store operated channel

SOCE:

Store operated Ca2+ entry

TRPC:

Transient receptor potential canonical

VSMC:

Vascular smooth muscle cells

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Acknowledgements

The author thanks Yingpei Zhang for technical assistance. This research was supported by the Intramural Research Program of the NIH (project Z01-ES-101684).

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Authors and Affiliations

  1. Department of Anatomy, College of Medicine, Huazhong University of Science and Technology, Wuhan, 430074, China

    Yanhong Liao

  2. Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health, 111 TW Alexander Dr., Research Triangle Park, NC, 27709, USA

    Joel Abramowitz & Lutz Birnbaumer

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  1. Yanhong Liao
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  2. Joel Abramowitz
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Correspondence to Yanhong Liao .

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Editors and Affiliations

  1. Laboratory Ion Channel Research, Campus Gasthuisberg, KU Leuven Department, Cell Mol Medicin, Leuven, Belgium

    Bernd Nilius

  2. Pharmakologie und Toxikologie, Universität des Saarlandes, Institut für Experimentelle u. Klinische, Homburg, Germany

    Veit Flockerzi

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Liao, Y., Abramowitz, J., Birnbaumer, L. (2014). The TRPC Family of TRP Channels: Roles Inferred (Mostly) from Knockout Mice and Relationship to ORAI Proteins. In: Nilius, B., Flockerzi, V. (eds) Mammalian Transient Receptor Potential (TRP) Cation Channels. Handbook of Experimental Pharmacology, vol 223. Springer, Cham. https://doi.org/10.1007/978-3-319-05161-1_14

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